The overall goal of the project is to determine how physiological regulators (hormones, pH, ions) and drugs which affect kidney functions interact with the cyclic nucleotide pathways. The focus of interest initially will be the cyclic nucleotide phosphodiesterases, which have differing specificities for cyclic AMP and cyclic GMP. We shall first purify and characterize each enzyme form. A method will next be developed to either physically separate or differentially inhibit the several enzymatic types and quantitate each separately. The distribution of each type in functionally differing regions of the mammalian kidney and the effects of possible regulators (vasopressin, parathormone, aldosterone, pH, calicum, magnesium, drugs)will be determined.